African-Americans bear the highest rates of hypertension in the world. The consequences of this burden are well known and include very high rates for stoke, heart disease, and renal disease. While we have made impressive gains in the understanding and treatment of hypertension, we have much more to do, especially among African-Americans. Thanks to the efforts of investigators at Johns Hopkins and many others, we now know many of the important exposures, but the allelic variants responsible for the predisposition to hypertension and its end-organ effects remain elusive. Therefore, we have designed, and begun to carry out, a family-based case-control study into the mechanism of hypertension emphasizing the genetic predisposition but including the environmental and cultural contexts. We hypothesize that common allelic variants of the genes encoding the G protein ?3 subunit, the ?-subunit of the adducin cytoskeletal protein, the ?2- adrenergic receptor, the a and ?-subunits of the epithelial sodium channel, angiotensin-converting enzyme, and angiotensinogen are associated and linked with blood pressure level among African-Americans.